Truncated Antibody Co-Binders for High-Affinity Binding
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Solution Overview
Problem
Producing antibodies and binding molecules with desired characteristics such as size, immunogenicity, binding affinity, and specificity remains a challenge in the field.
Innovation Solution
A co-binder molecule comprising a first binding moiety specifically recognizing a first target site and a second binding moiety specifically recognizing a second target site, where the second binding moiety is an antibody variable domain with an N-terminal truncation, connected through the N-terminus of the truncated domain via a linker.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional antibody variable domains are used in co-binders, then the structure is simpler to construct, but the binding affinity is lower (at least 3-fold lower than truncated versions)
Solution Approach 1:
The patent extracts and removes the N-terminal portion of the antibody variable domain to create a truncated version. This extraction of the N-terminal region (typically residues 1-5 or 1-10) results in a co-binder structure that achieves at least 3-fold higher binding affinity while maintaining sufficient structural functionality for antigen recognition and binding.
2Reliability
If binding sites overlap on the target molecule, then the co-binder structure is simpler, but the specificity is reduced
Solution Approach 1:
The patent applies local quality by ensuring that the first and second binding moieties recognize and bind to non-overlapping (distinct) target sites on the antigen. This spatial differentiation of binding sites enhances the specificity of the co-binder, allowing simultaneous binding to multiple distinct epitopes without steric interference or cross-competition, thereby improving diagnostic and therapeutic efficacy.
Data Source
AI summary
Provided herein, in some aspects, are binding molecules including co-binders having high affinity and/or high specificity to a target. In other aspects, provided herein are compositions, methods of making, and methods of using the binding molecules taught herein, such as diagnostic and therapeutic methods of use involving the co-binders taught herein